Hyperactivations frontales en mémoire de travail dans le trouble cognitif léger

Des études récentes ont rapporté que les individus âgés avec un trouble cognitif léger (TCL) ont de plus grandes activations en lien avec la réalisation d’une tâche cognitive que des personnes âgées saines. Des auteurs ont proposé que ces hyperactivations pourraient refléter des processus de plasticité cérébrale compensatoires ayant lieu pendant la phase précoce de la maladie d’Alzheimer. Des processus de compensations fonctionnelles pourraient émerger en réponse à une perte d’intégrité structurelle dans les régions du cerveau normalement requises pour compléter une tâche. Dans ce mémoire, j’ai évalué cette hypothèse chez des personnes avec TCL en faisant appel à une tâche de mémoire de travail comportant plusieurs niveaux de difficulté ainsi qu’aux techniques d’imagerie par résonnance magnétique (IRM) structurelle et fonctionnelle. Des analyses de régression multiples ont été utilisées afin d’identifier les régions cérébrales dont l’activité variait en fonction de l’intégrité neuronale telle que définie par le volume de l’hippocampe. Les valeurs estimées des paramètres du signal de ces régions furent ensuite extraites afin de procéder à des analyses corrélationnelles sur la performance ainsi que sur le volume de différentes structures cérébrales. Les résultats indiquent des hyperactivations dans les régions frontales droites chez les participants TCL souffrant d’une plus grande atteinte neuronale. De plus, le niveau d’activation est négativement corrélé au volume de structures frontales et pariétales. Ces résultats indique la présence d’une hyperactivation compensatoire dans la phase du TCL associée à la réalisation d’une tâche de mémoire de travail.

Hyperactivations frontales en mémoire de travail dans le trouble cognitif léger

Des études récentes ont rapporté que les individus âgés avec un trouble cognitif léger (TCL) ont de plus grandes activations en lien avec la réalisation d’une tâche cognitive que des personnes âgées saines. Des auteurs ont proposé que ces hyperactivations pourraient refléter des processus de plasticité cérébrale compensatoires ayant lieu pendant la phase précoce de la maladie d’Alzheimer. Des processus de compensations fonctionnelles pourraient émerger en réponse à une perte d’intégrité structurelle dans les régions du cerveau normalement requises pour compléter une tâche. Dans ce mémoire, j’ai évalué cette hypothèse chez des personnes avec TCL en faisant appel à une tâche de mémoire de travail comportant plusieurs niveaux de difficulté ainsi qu’aux techniques d’imagerie par résonnance magnétique (IRM) structurelle et fonctionnelle. Des analyses de régression multiples ont été utilisées afin d’identifier les régions cérébrales dont l’activité variait en fonction de l’intégrité neuronale telle que définie par le volume de l’hippocampe. Les valeurs estimées des paramètres du signal de ces régions furent ensuite extraites afin de procéder à des analyses corrélationnelles sur la performance ainsi que sur le volume de différentes structures cérébrales. Les résultats indiquent des hyperactivations dans les régions frontales droites chez les participants TCL souffrant d’une plus grande atteinte neuronale. De plus, le niveau d’activation est négativement corrélé au volume de structures frontales et pariétales. Ces résultats indique la présence d’une hyperactivation compensatoire dans la phase du TCL associée à la réalisation d’une tâche de mémoire de travail.

The Role of Existential Beliefs Within the Relation of Centenarians’ Health and Well-Being

The purpose of this study was to explore the role of existential beliefs in mediating the influence of health on centenarians' well-being. A total of 80 centenarians (mean age 101.1; SD = 1.3; 81.3 % women) with no/minor cognitive impairment were included. The OARS questionnaire for diseases and functional capacity (ADL, IADL), the Satisfaction with Life Scale, and the existential beliefs subscale were used for data collection. The findings suggest that existential resources are a crucial element for mitigating the impact of health constraints in subjective well-being in this population. Appropriate models of intervention for very old age that recognize the importance of religion, spirituality, and meaning of life are to be considered.

Growing up in a bubble: using germ-free animals to assess the influence of the gut microbiota on brain and behavior

There is a growing recognition of the importance of the commensal intestinal microbiota in the development and later function of the central nervous system. Research using germ-free mice (mice raised without any exposure to microorganisms) has provided some of the most persuasive evidence for a role of these bacteria in gut-brain signalling. Key findings show that the microbiota is necessary for normal stress responsivity, anxiety-like behaviors, sociability, and cognition. Furthermore, the microbiota maintains central nervous system homeostasis by regulating immune function and blood brain barrier integrity. Studies have also found that the gut microbiota influences neurotransmitter, synaptic, and neurotrophic signalling systems and neurogenesis. The principle advantage of the germ-free mouse model is in proof-of-principle studies and that a complete microbiota or defined consortiums of bacteria can be introduced at various developmental time points. However, a germ-free upbringing can induce permanent neurodevelopmental deficits that may deem the model unsuitable for specific scientific queries that do not involve early-life microbial deficiency. As such, alternatives and complementary strategies to the germ-free model are warranted and include antibiotic treatment to create microbiota-deficient animals at distinct time points across the lifespan. Increasing our understanding of the impact of the gut microbiota on brain and behavior has the potential to inform novel management strategies for stress-related gastrointestinal and neuropsychiatric disorders.

Effectiveness of non-pharmacological interventions to prevent falls in older people: a systematic overview. The SENATOR Project ONTOP Series

Background: Falls are common events in older people, which cause considerable morbidity and mortality. Non-pharmacological interventions are an important approach to prevent falls. There are a large number of systematic reviews of non-pharmacological interventions, whose evidence needs to be synthesized in order to facilitate evidence-based clinical decision making. Objectives: To systematically examine reviews and meta-analyses that evaluated non-pharmacological interventions to prevent falls in older adults in the community, care facilities and hospitals. Methods: We searched the electronic databases Pubmed, the Cochrane Database of Systematic Reviews, EMBASE, CINAHL, PsycINFO, PEDRO and TRIP from January 2009 to March 2015, for systematic reviews that included at least one comparative study, evaluating any non-pharmacological intervention, to prevent falls amongst older adults. The quality of the reviews was assessed using AMSTAR and ProFaNE taxonomy was used to organize the interventions. Results: Fifty-nine systematic reviews were identified which consisted of single, multiple and multi-factorial non-pharmacological interventions to prevent falls in older people. The most frequent ProFaNE defined interventions were exercises either alone or combined with other interventions, followed by environment/assistive technology interventions comprising environmental modifications, assistive and protective aids, staff education and vision assessment/correction. Knowledge was the third principle class of interventions as patient education. Exercise and multifactorial interventions were the most effective treatments to reduce falls in older adults, although not all types of exercise were equally effective in all subjects and in all settings. Effective exercise programs combined balance and strength training. Reviews with a higher AMSTAR score were more likely to contain more primary studies, to be updated and to perform meta-analysis. Conclusions: The aim of this overview of reviews of non-pharmacological interventions to prevent falls in older people in different settings, is to support clinicians and other healthcare workers with clinical decision-making by providing a comprehensive perspective of findings.

Lost in translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects

Background: Preclinical studies have identified certain probiotics as psychobiotics a live microorganisms with a potential mental health benefit. Lactobacillus rhamnosus (JB-1) has been shown to reduce stress-related behaviour, corticosterone release and alter central expression of GABA receptors in an anxious mouse strain. However, it is unclear if this single putative psychobiotic strain has psychotropic activity in humans. Consequently, we aimed to examine if these promising preclinical findings could be translated to healthy human volunteers. Objectives: To determine the impact of L. rhamnosus on stress-related behaviours, physiology, inflammatory response, cognitive performance and brain activity patterns in healthy male participants. An 8 week, randomized, placebo-controlled, cross-over design was employed. Twenty-nine healthy male volunteers participated. Participants completed self-report stress measures, cognitive assessments and resting electroencephalography (EEG). Plasma IL10, IL1β, IL6, IL8 and TNFα levels and whole blood Toll-like 4 (TLR-4) agonist-induced cytokine release were determined by multiplex ELISA. Salivary cortisol was determined by ELISA and subjective stress measures were assessed before, during and after a socially evaluated cold pressor test (SECPT). Results: There was no overall effect of probiotic treatment on measures of mood, anxiety, stress or sleep quality and no significant effect of probiotic over placebo on subjective stress measures, or the HPA response to the SECPT. Visuospatial memory performance, attention switching, rapid visual information processing, emotion recognition and associated EEG measures did not show improvement over placebo. No significant anti-inflammatory effects were seen as assessed by basal and stimulated cytokine levels. Conclusions: L. rhamnosus was not superior to placebo in modifying stress-related measures, HPA response, inflammation or cognitive performance in healthy male participants. These findings highlight the challenges associated with moving promising preclinical studies, conducted in an anxious mouse strain, to healthy human participants. Future interventional studies investigating the effect of this psychobiotic in populations with stress-related disorders are required.

Colon cancer surveillance in inflammatory bowel disease: unclear gain but no psychological pain?

BACKGROUND: Surveillance for colorectal neoplasia in inflammatory bowel disease (IBD) is widely practised despite a lack of convincing mortality reduction. The psychological impact of this approach is largely unexplored. AIM: To examine psychological well-being among IBD subjects undergoing colonoscopic surveillance for colorectal cancer (CRC). METHODS: A cross-sectional study was performed by interrogating an IBD database for subjects currently enrolled in colonoscopic surveillance programmes. Identified surveillance subjects were age- and gender-matched with IBD control subjects not meeting surveillance criteria. Subjects were mailed a questionnaire including demographic details, the Short Form 36 (SF-36) survey to assess quality of life, the Spielberger State-Trait Personality Inventory, the Multidimensional Health Locus of Control, and a Risk Perception Questionnaire. RESULTS: One hundred and thirty-nine of 286 (49%) subjects responded, 53% male, 46% Crohn disease. Fifty-six per cent respondents were in the surveillance group. Surveillance subjects were older (55.4 vs 51.1 years; P = .048) with longer disease duration, but otherwise had comparable demographics with controls. Overall, quality of life was not significantly different between cohorts (mean SF-36 63.82 vs 65.48; P = 0.70). Groups did not differ on any locus of control classification (P = 0.52), nor was there any difference between mean scores on 'state' subscales of the Spielberger State-Trait Personality Inventory: anxiety (P = 0.91), curiosity (P = 0.12), anger (P = 0.81) or depression (P = 0.70). Both groups grossly overestimated their perceived lifetime risk of CRC at 50%, with no difference between surveillance and control subjects (P = 1.0). CONCLUSIONS: Enrolment in colonoscopic colon cancer surveillance does not appear to impair psychological well-being in individuals with IBD despite longer disease duration. IBD patients overestimate their risk of CRC.

An investigation into the utility of the Mini Addenbrooke's Cognitive Examination (M-ACE) for the early detection of dementia and mild cognitive impairment in people aged 75 and over

Background/Aims: The Mini Addenbrooke’s Cognitive Examination (M-ACE) is the abbreviated version of the widely-used Addenbrooke’s Cognitive Examination (ACE-III), a cognitive screening tool that is used internationally in the assessment of mild cognitive impairment (MCI) and dementia. The objectives of this study were to investigate the diagnostic accuracy of the M-ACE with individuals aged 75 and over to distinguish between those who do and do not have a dementia or MCI, and also to establish whether the cut-off scores recommended by Hsieh et al. (2014) [9] in the original validation study for the M-ACE are optimal for this age group. Methods: The M-ACE was administered to 58 participants (24 with a diagnosis of dementia, 17 with a diagnosis of MCI and 17 healthy controls). The extent to which scores distinguished between groups (dementia, MCI or no diagnosis) was explored using receiver operating characteristic curve analysis. Results: The optimal cut-off for detecting dementia was ≤ 21/30 (score ≤ 21/30 indicating dementia with a sensitivity of 0.95, a specificity of 1 and a positive predictive value of 1) compared to the original higher published cut-off of ≤ 25/30 (sensitivity of 0.95, specificity of 0.70 and a positive predictive value of 0.82 in this sample). Conclusions: The M-ACE has excellent diagnostic accuracy for the detection of dementia in a UK clinical sample. It may be necessary to consider lower cut-offs than those given in the original validation study.

Registro de pacientes con distrofinopatías en Colombia

INTRODUCCIÓN. La distrofia muscular de Duchenne es una enfermedad neuromuscular con una herencia recesiva ligada al X que afecta a 1 de cada 3500 niños nacidos vivos. Se produce por mutaciones en el gen DMD que codifica para la distrofina. Se caracteriza por manifestaciones clínicas variables típicas de una distrofia muscular proximal progresiva. OBJETIVO. Realizar el primer registro en Colombia de los pacientes identificados con distrofinopatías, teniendo en cuenta características clínicas y paraclínicas, así como las mutaciones causales de esta patología. METODOLOGÍA Es un estudio descriptivo, transversal, de la revisión de historias clínicas de los pacientes con diagnóstico de DMD atendidos en la consulta de Genética de la Universidad del Rosario durante los años 2006 a 2015. RESULTADOS Se identificaron 99 pacientes, de los cuales 56 (56,56%) corresponden al fenotipo Duchenne y 12 (12,12%) al Becker. No fue posible clasificar a 31 pacientes (31,3%) por falta de datos clínicos. La edad de inicio de los síntomas fue en promedio de 4,41 años. Las mutaciones más frecuentes fueron las deleciones (69%), seguidas por las mutaciones puntuales(14%), las duplicaciones (11%) y por otras mutaciones (4%). CONCLUSIONES Este registro de distrofinopatías es el primero reportado en Colombia y el punto de partida para conocer la incidencia de la enfermedad, caracterización clínica y molecular de los pacientes, garantizando así el acceso oportuno a los nuevos tratamientos de medicina de precisión que permitan mejorar la calidad de vida de los pacientes y sus familias.

Qualidade de vida e aptidão física funcional dos idosos do concelho de Évora

Já na antiguidade o Homem se debruçava sobre a temática do envelhecimento, todavia os anos passaram e este fenómeno constitui-se como um dos assuntos da ordem do dia que nos abrange a todos, porque todos queremos vivenciar o prazer de envelhecer, à semelhança dos nossos antepassados. Porém estes procuravam o elixir de uma vida eterna e nós ambicionamos o elixir de uma longa vida com qualidade. Objectivo: Avaliar a qualidade de vida e aptidão física funcional dos idosos residentes do Concelho de Évora em instituições da rede solidária e nos seus domicílios com idade igual ou superior a 75 anos. Métodos: Após a selecção aleatória e tendo por base os critérios de exclusão (sem défice cognitivo avaliado pelo MMS e sem problemas físicos que impedissem de realizar os testes funcionais) aceitaram participar no estudo 396 idosos do Concelho de Évora dos quais 196 se encontram institucionalizados nos lares da rede solidária e 200 residem nos seus domicílios. Os instrumentos de avaliação utilizados foram o EASYcare e a bateria de testes Rikly Jones- Senior Fitness Test. Conclusões: Os idosos não institucionalizados apresentam melhor qualidade de vida e aptidão física funcional face aos idosos institucionalizados. Os níveis de incapacidade do grupo de idosos são baixos, o que revela que estamos perante um grupo maioritariamente independente. Por sua vez os homens apresentam melhor auto­ percepção da sua qualidade de vida e melhor desempenho nos testes físicos realizados. Com o processo de envelhecimento é notório uma avaliação inferior nas diferentes áreas da qualidade de vida por parte dos idosos assim como um pior desempenho nos testes físicos. Verificou-se também que existem correlações significativas entre as áreas da qualidade de vida avaliadas e os parâmetros de aptidão física funcional considerados, estando estes interrelacionados. ABSTRACT: Introduction: Already in the antiquity Man was dealing with the aging topic, however the years passed and this issue is as one of the topics on the agenda that covers everyone, because we all want to experience the pleasure of growing old, like of our ancestors. Although they sought the elixir of eternal life and we are aiming the elixir of long life with quality. Aim: To evaluate the quality of life and functional fitness of elderly aged over 75 years, residents of the Municipality of Évora in the network institutions in their households. Methods: After random selection and based on the exclusion criteria (no cognitive impairment assessed by MMS and no conditions that hamper them from performing functional tests) agreed to participate in the study 396 elderly from Évora's Municipality of which 196 are institutionalized in nursing homes network of solidarity and 200 reside in their homes. The assessment instruments used were the EASYcare and battery of tests Rikly Jones- Senior Fitness Test. Conclusions: The non-institutionalized elderly have a better quality of life and functional fitness in relation to the institutionalized elderly. The levels of disability in the elderly group are low, indicating that this is a group mostly independent. ln tum the men have better self-perception of their quality of life and better performance in physical tests performed. With the aging process is an assessment of less known in different areas of life quality for elderly people as well as a poorer performance in physical tests. There was also that there are significant correlations between the areas of quality of life and evaluated the parameters of functional fitness considered and these interrelated.

Failure of a numerical quality assessment scale to identify potential risk of bias in a systematic review: a comparison study

BACKGROUND: Assessing methodological quality of primary studies is an essential component of systematic reviews. Following a systematic review which used a domain based system [United States Preventative Services Task Force (USPSTF)] to assess methodological quality, a commonly used numerical rating scale (Downs and Black) was also used to evaluate the included studies and comparisons were made between quality ratings assigned using the two different methods. Both tools were used to assess the 20 randomized and quasi-randomized controlled trials examining an exercise intervention for chronic musculoskeletal pain which were included in the review. Inter-rater reliability and levels of agreement were determined using intraclass correlation coefficients (ICC). Influence of quality on pooled effect size was examined by calculating the between group standardized mean difference (SMD).

RESULTS: Inter-rater reliability indicated at least substantial levels of agreement for the USPSTF system (ICC 0.85; 95% CI 0.66, 0.94) and Downs and Black scale (ICC 0.94; 95% CI 0.84, 0.97). Overall level of agreement between tools (ICC 0.80; 95% CI 0.57, 0.92) was also good. However, the USPSTF system identified a number of studies (n = 3/20) as "poor" due to potential risks of bias. Analysis revealed substantially greater pooled effect sizes in these studies (SMD -2.51; 95% CI -4.21, -0.82) compared to those rated as "fair" (SMD -0.45; 95% CI -0.65, -0.25) or "good" (SMD -0.38; 95% CI -0.69, -0.08).

CONCLUSIONS: In this example, use of a numerical rating scale failed to identify studies at increased risk of bias, and could have potentially led to imprecise estimates of treatment effect. Although based on a small number of included studies within an existing systematic review, we found the domain based system provided a more structured framework by which qualitative decisions concerning overall quality could be made, and was useful for detecting potential sources of bias in the available evidence.

Development and validation of the Overall Personality Assessment Scale (OPERAS)

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Assessment of surface winds over the Atlantic, Indian and Pacific Ocean sectors of the Southern Ocean in CMIP5 models: historical bias, forcing response, and state dependence

An assessment of the fifth Coupled Models Intercomparison Project (CMIP5) models’ simulation of the near-surface westerly wind jet position and strength over the Atlantic, Indian and Pacific sectors of the Southern Ocean is presented. Compared with reanalysis climatologies there is an equatorward bias of 3.7° (inter-model standard deviation of ± 2.2°) in the ensemble mean position of the zonal mean jet. The ensemble mean strength is biased slightly too weak, with the largest biases over the Pacific sector (-1.6±1.1 m/s, 27 -22%). An analysis of atmosphere-only (AMIP) experiments indicates that 41% of the zonal mean position bias comes from coupling of the ocean/ice models to the atmosphere. The response to future emissions scenarios (RCP4.5 and RCP8.5) is characterized by two phases: (i) the period of most rapid ozone recovery (2000-2049) during which there is insignificant change in summer; and (ii) the period 2050-2098 during which RCP4.5 simulations show no significant change but RCP8.5 simulations show poleward shifts (0.30, 0.19 and 0.28°/decade over the Atlantic, Indian and Pacific sectors respectively), and increases in strength (0.06, 0.08 and 0.15 m/s/decade respectively). The models with larger equatorward position biases generally show larger poleward shifts (i.e. state dependence). This inter-model relationship is strongest over the Pacific sector (r=-0.89) and insignificant over the Atlantic sector (r=-0.50). However, an assessment of jet structure shows that over the Atlantic sector jet shift is significantly correlated with jet width whereas over the Pacific sector the distance between the sub-polar and sub-tropical westerly jets appears to be more important.

Controlling for culture-specific response bias using ipsatization and response style indicators: Family orientation in seventeen cultures and two generations

Within-subject standardization (ipsatization) has been advocated as a possible means to control for culture-specific responding (e.g., Fisher, 2004). However, the consequences of different kinds of ipsatization procedures for the interpretation of mean differences remain unclear. The current study compared several ipsatization procedures with ANCOVA-style procedures using response style indicators for the construct of family orientation with data from 14 cultures and two generations from the Value-of-Children-(VOC)-Study (4135 dyads). Results showed that within-subject centering/standardizing across all Likert-scale items of the comprehensive VOC-questionnaire removed most of the original cross-cultural variation in family orientation and lead to a non-interpretable pattern of means in both generations. Within-subject centering/standardizing using a subset of 19 unrelated items lead to a decrease to about half of the original effect size and produced a theoretically meaningful pattern of means. A similar effect size and similar mean differences were obtained when using a measure of acquiescent responding based on the same set of items in an ANCOVA-style analysis. Additional models controlling for extremity and modesty performed worse, and combinations did not differ from the acquiescence-only model. The usefulness of different approaches to control for uniform response styles (scalar equivalence not given) in cross- cultural comparisons is discussed.

On the validity of measuring change over time in routine clinical assessment: a close examination of item-level response shifts in psychosomatic inpatients

Objective: Significant life events such as severe health status changes or intensive medical treatment often trigger response shifts in individuals that may hamper the comparison of measurements over time. Drawing from the Oort model, this study aims at detecting response shift at the item level in psychosomatic inpatients and evaluating its impact on the validity of comparing repeated measurements. Study design and setting: Complete pretest and posttest data were available from 1188 patients who had filled out the ICD-10 Symptom Rating (ISR) scale at admission and discharge, on average 24 days after intake. Reconceptualization, reprioritization, and recalibration response shifts were explored applying tests of measurement invariance. In the item-level approach, all model parameters were constrained to be equal between pretest and posttest. If non-invariance was detected, these were linked to the different types of response shift. Results: When constraining across-occasion model parameters, model fit worsened as indicated by a significant Satorra–Bentler Chi-square difference test suggesting potential presence of response shifts. A close examination revealed presence of two types of response shift, i.e., (non)uniform recalibration and both higher- and lower-level reconceptualization response shifts leading to four model adjustments. Conclusions: Our analyses suggest that psychosomatic inpatients experienced some response shifts during their hospital stay. According to the hierarchy of measurement invariance, however, only one of the detected non-invariances is critical for unbiased mean comparisons over time, which did not have a substantial impact on estimating change. Hence, the use of the ISR can be recommended for outcomes assessment in clinical routine, as change score estimates do not seem hampered by response shift effects.